Fluid mechanics of flow through microchannels

The main objective of this thesis is to characterize and investigate single-phase liquid flow in microchannels, and can be divided into two parts: analytical modeling and experimental investigation. In the analytical part, velocity distribution and Darcy friction factor of liquid flow in both parallel-plate and rectangular microchannels were revised theoretically by taking into account the effects of slip boundary conditions as well as the aspect ratio of the channels. The combined effects of changing relative spacing, eccentricity, and viewing directions on the wetting conditions of the fabricated micropillar surfaces were experimentally investigated. The equilibrium 3D shape of the droplet on anisotropic surfaces was also examined. The wettability of microhole structures fabricated by replica molding of polydimethylsiloxane (PDMS) was analyzed by measuring both static and dynamic contact angles and it was found that wetting conditions can be controlled not only by changing the normalized widths but also the eccentricities. Generally, increasing the micropattern eccentricity increased the contact angle hysteresis. Dependency of the contact angle hysteresis on microhole eccentricity was explained by the shape of the three-phase contact line on microhole configurations. Drag reduction of microchannels with microhole arrays efficiency was evaluated. The results indicated that the impact of microhole eccentricity on drag reduction performance correlated well with the contact angle hysteresis, rather than the static contact angle. These findings provide additional insights in design and fabrication of efficient micropatterned channels for reducing the flow resistance.DOCTOR OF PHILOSOPHY (MAE

Inventions and Innovations in Preclinical Platforms for Cancer Research

Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumour models. The complex tumour microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed

Prediction of Dispersion Rate of Airborne Nanoparticles in a Gas-Liquid Dual-Microchannel Separated by a Porous Membrane: A Numerical Study

Recently, there has been increasing attention toward inhaled nanoparticles (NPs) to develop inhalation therapies for diseases associated with the pulmonary system and investigate the toxic effects of hazardous environmental particles on human lung health. Taking advantage of microfluidic technology for cell culture applications, lung-on-a-chip devices with great potential in replicating the lung air–blood barrier (ABB) have opened new research insights in preclinical pathology and therapeutic studies associated with aerosol NPs. However, the air interface in such devices has been largely disregarded, leaving a gap in understanding the NPs’ dynamics in lung-on-a-chip devices. Here, we develop a numerical parametric study to provide insights into the dynamic behavior of the airborne NPs in a gas–liquid dual-channel lung-on-a-chip device with a porous membrane separating the channels. We develop a finite element multi-physics model to investigate particle tracing in both air and medium phases to replicate the in vivo conditions. Our model considers the impact of fluid flow and geometrical properties on the distribution, deposition, and translocation of NPs with diameters ranging from 10 nm to 900 nm. Our findings suggest that, compared to the aqueous solution of NPs, the aerosol injection of NPs offers more efficient deposition on the substrate of the air channel and higher translocation to the media channel. Comparative studies against accessible data, as well as an experimental study, verify the accuracy of the present numerical analysis. We propose a strategy to optimize the affecting parameters to control the injection and delivery of aerosol particles into the lung-on-chip device depending on the objectives of biomedical investigations and provide optimized values for some specific cases. Therefore, our study can assist scientists and researchers in complementing their experimental investigation in future preclinical studies on pulmonary pathology associated with inhaled hazardous and toxic environmental particles, as well as therapeutic studies for developing inhalation drug delivery

Eccentricity effects of microhole arrays on drag reduction efficiency of microchannels with a hydrophobic wall

This paper experimentally investigates the effects of microhole eccentricity on the slip lengths of Stokes flow in microchannels with the bottom wall made of microhole arrays. The wettability of such microhole structures fabricated by the replica molding of polydimethylsiloxane is first analyzed measuring both static and dynamic contact angles. Subsequently, the drag reduction performance of the microchannels with such hydrophobic microhole surfaces is evaluated. The results indicate that the impact of microhole eccentricity on drag reduction performance correlates well with the contact angle hysteresis rather than with the static contact angle. Furthermore, microhole arrays with large normalized width and zero eccentricity show the minimum contact angle hysteresis of 18.7°. In these microchannels, the maximum percentage increase in the relative velocity is 39% corresponding to a slip length of 2.49 μm. For the same normalized width, increasing the normalized eccentricity to 2.6 increases the contact angle hysteresis to 36.5° that eventually reduces the percentage increase in relative velocity and slip length down to 16% and 0.91 μm, respectively. The obtained results are in qualitative agreement with the existing theoretical and numerical models. These findings provide additional insights in the design and fabrication of efficient micropatterned channels for reducing the flow resistance, and leave open questions for theoreticians to further investigate in this field.Published versio

Eccentricity effect of micropatterned surface on contact angle

This article experimentally shows that the wetting property of a micropatterned surface is a function of the center-to-center offset distance between successive pillars in a column, referred to here as eccentricity. Studies were conducted on square micropatterns which were fabricated on a silicon wafer with pillar eccentricity ranging from 0 to 6 μm for two different pillar diameters and spacing. Measurement results of the static as well as the dynamic contact angles on these surfaces revealed that the contact angle decreases with increasing eccentricity and increasing relative spacing between the pillars. Furthermore, quantification of the contact angle hysteresis (CAH) shows that, for the case of lower pillar spacing, CAH could increase up to 41%, whereas for the case of higher pillar spacing, this increment was up to 35%, both corresponding to the maximum eccentricity of 6 μm. In general, the maximum obtainable hydrophobicity corresponds to micropillars with zero eccentricity. As the pillar relative spacing decreases, the effect of eccentricity on hydrophobicity becomes more pronounced. The dependence of the wettability conditions of the micropatterned surface on the pillar eccentricity is attributed to the contact line deformation resulting from the changed orientation of the pillars. This finding provides additional insights in design and fabrication of efficient micropatterned surfaces with controlled wetting properties

Analytical and numerical investigations of the effects of microchannel aspect ratio on velocity profile and friction factor

This study presents a new form of velocity distribution in laminar liquid flow in rectangular microchannels using the eigenfunction expansion technique. Darcy friction factor and Poiseuille number are also obtained analytically. Due to the symmetry of the solutions, the effects of changing the aspect ratio from 0 to ∞ are also discussed. Using finite element method (FEM), the obtained analytical results are further compared with the 3D numerical simulations for the rectangular microchannels with different range of aspect ratio and pressure gradient, and excellent agreements were found. These findings provide additional insights in interpreting the results of the pressure driven flows in finite aspect ratio microchannels, in which very precise comparison with the macroscale theory is crucial

Fluid mechanics of flow through rectangular hydrophobic microchannels

In this study, the effect of two important parameters have been evaluated for pressure driven liquid flows in microchannel in laminar regime by analytical modeling, followed by experimental measurement. These parameters are wettability conditions of microchannel surfaces and aspect ratio of rectangular microchannels. For small values of aspect ratio, the channel was considered to a have rectangular cross-section, instead of being two parallel plates. Novel expressions for these kinds of channels were derived using Eigen function expansion method. The obtained two-dimensional solutions based on dual finite series were then extended to the case of a constant slip velocity at the bottom wall. In addition, for large values of aspect ratio, a general equation was obtained which is capable of accounting for different values of slip lengths for both upper and lower channel walls. Firstly, it was found that for low aspect ratio microchannels, the results obtained by analytical rectangular 2-D model agree well with the experimental measurements as compared to one dimensional solution. For high aspect ratio microchannels, both models predict the same trend. This finding indicates that using the conventional 1-D solution may not be accurate for the channels where the width is of the same order as the height. Secondly, experimental results showed that up to 2.5% and 16% drag reduction can be achieved for 1000 and 250 micron channel height, respectively. It can be concluded that increasing the surface wettability can reduce the pressure drop in laminar regime and the effect is more pronounced by decreasing the channel height

Anti-Cancer Drug Screening with Microfluidic Technology

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high-throughput drug screening, require a small number of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. Many attempts have been made in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development

Engineering Micropatterned Surfaces for Controlling the Evaporation Process of Sessile Droplets

Controlling the evaporation process of a droplet is of the utmost importance for a number of technologies. Also, along with the advances of microfabrication, micropatterned surfaces have emerged as an important technology platform to tune the wettability and other surface properties of various fundamental and applied applications. Among the geometrical parameters of these micropatterns, it is of great interest to investigate whether the arrangement of the patterns would affect the evaporation process of a sessile liquid droplet. To address this question, we fabricated four microhole arrays with different arrangements, quantified by the parameter of “eccentricity”. The results suggested that, compared to smooth substrates, the evaporation mode was not only affected by engineering the microhole arrays, but also by the eccentricity of these micropatterns. The values of contact angle hysteresis (CAH) were used to quantify and test this hypothesis. The CAH could partially explain the different evaporation modes observed on the microhole arrays with zero and non-zero values of eccentricity. That is, on microhole arrays with zero eccentricity, CAH of water droplets was comparatively low (less than 20 ° ). Consistently, during the evaporation, around 60% of the life span of the droplet was in the mixed evaporation mode. Increasing the eccentricity of the microhole arrays increases the values of CAH to above 20 ° . Unlike the increasing trend of CAH, the evaporation modes of sessile droplets on the microhole array with non-zero values of eccentricity were almost similar. Over 75% of the life span of droplets on these surfaces was in constant contact line (CCL) mode. Our findings play a significant role in any technology platform containing micropatterned surfaces, where controlling the evaporation mode is desirable

Analytical modeling of slip flow in parallel-plate microchannels

This paper presents analytical modeling of slip liquid flow in parallel-plate microchannels, and can be divided in two parts. In the first part, classical relationships describing velocity, flow rate, pressure gradient, and shear stress are extended to the more general cases where there exist two different values of the yet-unknown slip lengths at the top and bottom walls of the channel. These formulations can be used to experimentally determine the values of slip length on the channels fabricated from two different hydrophobic walls. In the second part, the emphasis is given on the quantification of the slip length analytically. Generating mechanism of slip is attributed to the existence of a low-viscosity region between the liquid and the solid surface. By extending the previous works, the analytical values of slip length are determined using exact, rather than empirical, values of air gap thickness at different ranges of air flow Knudsen number. In addition to the exact expressions of air gap thickness, the corresponding ranges of the channel height where slip flow can be induced are also found analytically. It is found that when the channel height is larger than 700 μ m, air flow is in continuum regime and no-slip boundary condition can be used. For the case where the channels height is smaller than 700 μ m, and larger than 7.5 μm, slip boundary condition should be used to model the air flow in the channel. Finally, for the channel with the height smaller than 7.5 μm, Navier-Stokes equation cannot be used to model the air flow, and instead molecularbased approaches should be implemented. The results of this paper can be used as a guideline for both experimentalists and theoreticians to study the slip flow in parallel-plate microchannels